This phase II trial studies how well combination chemotherapy with or without oregovomab followed by stereotactic body radiation therapy (SBRT) and nelfinavir mesylate works in treating patients with pancreatic cancer that has spread to nearby organs or tissues. Drugs used in chemotherapy, such as gemcitabine hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as oregovomab, can block tumor growth by targeting certain cells. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs, such as nelfinavir mesylate, may make tumor cells more sensitive to radiation therapy. Giving combination chemotherapy with or without oregovomab followed by SBRT and nelfinavir mesylate may kill more tumor cells.

A Phase II Study of Neoadjuvant Chemotherapy With and Without Immunotherapy to CA125 (Oregovomab) Followed by Hypofractionated Stereotactic Radiotherapy and Concurrent HIV Protease Inhibitor Nelfinavir in Patients With Locally Advanced Pancreatic Cancer

Rate of progressive disease, defined as at least a 25% increase in the longest diameter of a lesion, taking as reference the longest diameter recorded since the treatment started [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]

Failure-free survival [ Time Frame: Date of administration study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 5 years ] [ Designated as safety issue: No ]

Analyzed using Kaplan-Meier plots, medians and ranges.

Incidence of toxicity, graded by the National Cancer Institute Common Toxicity Criteria version 4.0, reported by frequency and severity [ Time Frame: Up to 30 days after the final dose of study drug ] [ Designated as safety issue: Yes ]

Adverse events will be tallied for overall frequency (number and percentage of subjects), worst reported severity, and relationship to study drugs. Serious adverse events will be summarized similarly.

Local control [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

The proportion of patients responding will be summarized using frequencies and percentages.

Tumor response rate, evaluated on the pathology specimen [ Time Frame: Up to week 18 ] [ Designated as safety issue: No ]

The proportion of patients responding will be summarized using frequencies and percentages.

Other Outcome Measures:

Change in proportion of patients with cellular immune response, defined as having a significant increase from baseline in CA125 enzyme-linked immunosorbent spot [ Time Frame: Baseline to up to week 12 ] [ Designated as safety issue: No ]

Defined relative to baseline according to the permutation test The proportion of patients responding will be summarized using frequencies and percentages.

I. To assess the safety of neoadjuvant chemotherapy, (gemcitabine, leucovorin, 5-FU) with or without oregovomab, followed by SRT concurrently with nelfinavir in patients with locally advanced pancreatic cancer that is CA125 positive (>= 10) or CA125 negative (< 10).

II. To assess the cellular and humoral immune responses to active immunotherapy with oregovomab/monoclonal antibody in patients with pancreas cancer with CA125 level greater than 10 undergoing chemotherapy and radiation treatments.

TERTIARY OBJECTIVES:

I. To evaluate tumor and organ motion with 4-dimensional (4D) computed tomography (CT) and respiratory gating system and to evaluate the effect of tumor/organ motion on the dosimetry, local control and survival.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Eligibility

Ages Eligible for Study:

19 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Pathologically confirmed adenocarcinoma of the pancreas; patients have resectable or borderline resectable disease with no evidence of distant metastases; the maximum dimension of the tumor must be =< 10 cm

Karnofsky performance status of 60% or better

Patients who received chemotherapy > 5 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry

Patients who received radiation therapy > 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry

All malignant disease must be able to be encompassed within a single irradiation field

All patients must have radiographically assessable disease

Absolute neutrophil count (ANC) greater than or equal to 1500/uL

Platelet count greater than or equal to 100,000/uL

Serum creatinine less than or equal to 2.0 mg/dL

Total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction; if the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of biliary stent (7 French or greater) or percutaneous transhepatic drainage are acceptable; once biliary drainage has been established, institution of gemcitabine therapy may proceed when the total bilirubin falls to =< 4.0 mg/dL; patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation

The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

No prior therapy with the exception of 1 cycle of chemotherapy based on current diagnosis and clinical condition

Patients must have CA125 level >= 10 to participate in the immunotherapy aspect of the trial and receive oregovomab; if the patient has CA125 >= 10 who is not eligible to receive oregovomab (e.g. allergic to the drug) but is eligible for the rest of treatment, this patient should be accrued to the part of protocol without oregovomab

Exclusion Criteria:

Patients who cannot undergo staging laparoscopy; for example, this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or potentially harmful; the patient is eligible if they have a common bile duct stent adjacent to the tumor that may be used as an internal marker, or if the patient has already had a staging laparoscopy without marker implantation and the markers can be implanted (by interventional radiology) prior to the beginning of radiation therapy

Patients with a known allergy to murine proteins or have had a documented anaphylactic reaction or allergy to any of chemotherapy agents used in this protocol, oregovomab, or to antiemetics appropriate for administration in conjunction with protocol-directed therapy

Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safety

Pregnant and nursing women are excluded from this study

Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years

Patients with active duodenal ulcer or bleeding or history of a gastrointestinal fistula or perforation or other significant bowel problems (severe nausea, vomiting, inflammatory bowel disease and significant bowel resection)

Patients with a recognized acquired, hereditary, or congenital immunodeficiency disease including cellular immunodeficiency's, hypogammaglobulinemia or dysgammaglobulinemia

Patients receiving the following drugs that are contraindicated with nelfinavir (NFV) (VIRACEPT) will be excluded if they cannot be change or discontinued; drugs that should not be coadministered with Viracept:

Anti-mycobacterial: rifabutin; it is recommended that the dose of rifabutin be reduced to one-half the usual dose when administered with VIRACEPT; 1250 mg BID is the preferred dose of VIRACEPT when coadministered with rifabutin

Erectile dysfunction agent: sildenafil; sildenafil shall not exceed a maximum single dose of 25 mg in a 48 hour period

HMG-CoA reductase inhibitor: atorvastatin; use lowest possible dose of atorvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as pravastatin or fluvastatin in combination with VIRACEPT

Immunosuppressants: cyclosporine, tacrolimus, sirolimus

Narcotic analgesic: methadone; dosage of methadone may need to be increased when coadministered with VIRACEPT

Oral contraceptive: ethinyl estradiol; alternative or additional contraceptive measures should be used when oral contraceptives and VIRACEPT are coadministered

Macrolide antibiotic: azithromycin; dose adjustment of azithromycin is not recommended, but close monitoring for known side effects such as liver enzyme abnormalities and hearing impairment is warranted

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01959672